As a result of environmental exposure and slow excretion there is a high cadmium burden in the entire population. A suggested relationship between cadmium exposure and hypertension makes the study of chronic cadmium exposure of great public health significance. We have recently discovered that cadmium causes increased arterial reactivity to adrenergic stimulation in the rat. We propose the following study: 1. Determine if the enhanced vascular responsiveness to norepinephrine is associated with the development of hypertension; 2. Define a cadmium exposure regimen which will consistently lead to increased vascular reactivity and hypertension; 3. Determine if the enhanced vascular reactivity includes increased responsiveness to other vasoactive agents; 4. Determine if there are other factors altered by cadmium such as renal salt retention; 5. Determine whether a genetic predisposition to hypertension influences the response to cadmium; 6. Establish the mechanism of vascular effect of cadmium. Rats will be exposed to various regimens of cadmium for periods of 1 week to 1 year. Blood pressure and vascular reactivity will be measured in vivo. In vitro work will include isolated arteries removed from cadmium-exposed rats as well as preparations to which cadmium will be added in vitro. Part of the studies will be done in spontaneously hypertensive rats to determine the possible genetic contribution to the vascular effects of cadmium. These studies should clarify the relationship between cadmium and hypertensive disease, and should also provide information regarding mechanism by which hypertension develops.